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Prostatic Nerve Growth Factor Inducible A Gene Binds a Novel Element in the Retinoblastoma Gene Promoter¹

Division of Urology, Washington University School of Medicine [M. L. D.] at Jewish Hospital [S. W., J. W. B.], St. Louis, Missouri 63110

² To whom requests for reprints should be addressed, at Washington University School of Medicine, Department of Surgery, Division of Urology, Washington University Medical Center, 4960 Childrens Place, St. Louis, MO 63110.

We are investigating the role of the early response transcription factor, nerve growth factor inducible A gene (NGFI-A), as a modulator of retinoblastoma (RB) gene transcription in prostate cells. Examination of the RB promoter reveals a novel element GCGGGGGAG located at nucleotides 152–144 upstream of the methionine initiation codon. This sequence shares strong homology with the consensus NGFI-A binding element GCGGGGGCG varying by a single nucleotide. In DNA binding assays, an NGFI-A fusion protein and the native protein product of the NGFI-A gene purified from prostate cancer cells bound specifically to an oligonucleotide containing the RB promoter element. Gene expression studies in rat ventral prostate demonstrated a 1.9-fold increase in RB mRNA following castration that parallels a 2.7-fold induction of NGFI-A mRNA. In summary, the in vitro DNA binding data and the transient coregulation of rat NGFI-A and RB following castration suggests that the RB gene may be transcriptionally regulated by NGFI-A in prostate cells.

¹ This study was supported in part by Grant IN-36-34 from the American Cancer Society and by Grant P20 CA 58193 from the NCI.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/29/93. Accepted 10/19/93.

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